AstraZeneca Symbicort Production Facility, Dunkirk, France

AstraZeneca France's Dunkirk plant has been upgraded and expanded for the manufacture of the blockbuster asthma and Chronic Obstructive Pulmonary Disease (COPD) drug, Symbicort.

AstraZeneca France announced a major expansion to their pharmaceutical production facilities in May 2004. The plant was first built in 1991 at a cost of $550 million. The construction phase of the 2004-05 expansion was completed in February 2005 and the validation of the new manufacturing facilities was completed in August 2005. The expansion cost an estimated €90 million and was supported by grant aid from regional authorities in Normandy, including IFA and Nord France Experts.

Symbicort generated worldwide sales of more than $549 million in 2003. The drug is dispensed using a dry powder inhaler called the Turbuhaler. The method of dispensing the drug is set to change to use a new high tech pressurised Metered Dose Inhaler (pMDI).

The Dunkirk facilities were upgraded for two major reasons. Firstly, the quantities of Symbicort produced at the plant will increase significantly so that the plant becomes the major manufacturing site for this drug. Secondly, the new pMDI will be filled and finished at the plant as well using state-of-the-art Class 100,000 cleanroom facilities. The pMDI treatment was filed for approval with the European Regulatory Authorities in July 2004. The facility, which already employed 630 personnel, has increased its workforce by a further 150 manufacturing personnel.

NEW AEROSOL FACILITIES ENGINEERING

Jacobs Engineering Group Inc of Pasedena, USA, won the contract to provide Engineering, Procurement, Construction (EPC) as well as project management and validation for the new aerosol production line. This line cost $25 million. The project was completed under a fast-track basis to accommodate an anticipated increased global demand for Symbicort in 2005.

The new 900m² cleanroom (Class 100,000) facility at the plant - to contain the fill and finish section of the production line - was constructed by Carmetec of Uppsala, Sweden. Carmetec supplied, constructed and validated the cleanroom facility in early 2005. The fill and finish manufacturing equipment was installed shortly after. The increased production capacity at the Dunkirk site will also be used for the production of clinical quantities of new products due for release in the future.

SYMBICORT AND METERED DOSE DELIVERY

Symbicort is a combination therapy containing the corticosteroid budesonide and the rapid- and long-acting bronchodilator formoterol in a single inhaler therapy (Turbuhaler). The drug is indicated in the regular treatment of asthma and COPD, where use of a combination of inhaled glucocorticosteroid and long acting beta-agonist (B2) is appropriate.

The product is available as the Symbicort Turbuhaler in both standard dose (160/4.5µg) and low-dose (80/4.5µg) strengths and is approved for use in 90 countries worldwide and launched in 70. The drug will soon be available in the new pressurised Metered Dose Inhaler (pMDI) to suit new patient preferences.

The system will offer easily adjustable dosing, which will enable doctors to tailor a patient's treatment with a single inhaler for all situations (baseline therapy, increasing the dose during worsening attacks, acute situations), thereby achieving greater efficacy than with fixed doses.

The new generation of respiratory pMDIs are to use new HFC (hydrofluorocarbon) propellants; these are more environmentally friendly than the previous CFC (chlorofluorocarbon) propellants and will not damage or deplete the ozone layer. The pMDI has some advantages over the Turbuhaler in that the delivery of medication is not breath-dependent - the dose may be controlled according to requirement and the system is easier to use.

In January 2005 results from the STAY (US) trial were published in the American Journal of Respiratory and Critical Care Medicine. Data showed that Symbicort Single inhaler Therapy (SiT) achieved a 45% reduction in the frequency of severe asthma attacks. In Europe, in November 2004, the regulatory application for Symbicort SiT was withdrawn to allow more data to be submitted. A new regulatory filing for Europe was submitted in the summer of 2005 containing additional data from further ongoing studies, including in total 13,000 patients with mild to moderate asthma.