Trygg Pharma’s Seal Sands Bulk Pharmaceuticals Facility, Teesside, UK

The administrative building at Lundbeck's synthesis factory on Teesside, in north-east England.

The tank farm at Lundbeck's escitalopram synthesis factory in north-east England.

Work on the construction of the production unit, named P7, commenced in Seal Sands in May 2000.

Tank farm at the facility.

The Seal Sands production site was equipped to produce escitalopram (the S enantiomer), a selective serotonin reuptake inhibitor that is marketed under the brand name Cipralex.

Chemical structure of escitalopram (S enantiomer).

In April 2000, Lundbeck Pharmaceuticals was awarded contracts for the construction of a bulk pharmaceutical facility in Seal Sands, Teesside, UK.

Construction started in May 2000 and the plant was opened in 2002. Production reached full scale by January 2003.

The $80m (£53m) facility was purpose-built to synthesise escitalopram, the active ingredient in Lundbeck’s anti-depressant drug Cipralex. It used state-of-the-art chromatographic separation technology in the form of a large-scale simulated moving bed unit, claimed to be the largest in the world.

Lundbeck Pharmaceuticals is the UK subsidiary of H Lundbeck of Denmark.

Closure and acquisition of Seal Sands

In 2008, the production site at Seal Sands was closed for developing an optimised production process. Instead of having three factories, Lundbeck consolidated its in-house active pharmaceutical ingredients (API) production at two factories in Italy and Denmark.

Production at the Seal Sand manufacturing facility was partly shifted to Lundbeck’s manufacturing plants in Italy and Denmark.

In July 2011, after being closed for nearly three years, the Seal Sands plant was acquired by Norwegian Trygg Pharma for $22m (£14m).

Trygg Pharma is jointly owned by Oslo-based Aker Biomarine and US-based private equity firm Lindsay Goldberg. More than 65 people lost their jobs when the plant was shut down in 2008 and the acquisition will initially create around 25 jobs. Trygg Pharma is committed to expanding the facility in future.

Escitalopram synthesis facility contractors and construction

Foster Wheeler was awarded the contract for the project management, engineering design, equipment procurement, commissioning and validation of the new facility.

Foster Wheeler’s Reading-based pharmaceutical Centre of Excellence was in charge of the preliminary project design. Tilbury Douglas was awarded the contract for construction work on the plant.

Shepherd Engineering Services was awarded a £2.5m contract for mechanical and electrical design and installation. The simulated moving bed unit was designed, constructed and installed by Novasep of Nancy in France. Foster Wheeler was required to complete operational qualification of the plant within 20 months.

As the site was located in a low-lying area, the first project requirement was for the site to be raised by 1m to secure the land and prevent flooding. This was accomplished by the use of 30,000t of stone backfill material.

The project required the construction of two new process buildings, a new utility building, a tank farm and all associated site infrastructure. The buildings were all constructed using drywall stud steel partitioning for the internal walls and a new system of stainless steel wall plates, which also act as conduits for building services (electrical, water, steam).

One production building housed 15 reactors, 17 receivers and two filter driers. The other process building contained the largest simulated moving bed chromatographic separation unit manufactured for pharmaceutical separations, the Lico Sep 6-800, which consists of six 800mm internal diameter columns.

Simulated moving bed chromatography

Simulated moving bed chromatography with the Lico Sep 6-800 made use of six chiral chromatographic columns of 800mm ID linked in a continuous fashion. The mixture is introduced into the cycle in a suitable solvent and the mixture chromatographically separates and is monitored.

The pure required enantiomer can be drawn off and any unwanted impure material recycled again in a continuous process. Eventually, the process must allow the unwanted enantiomer to be removed and recycled into the manufacturing process so as not to waste valuable starting material.

Lundbeck’s purification process of escitalopram, including chromatographic continuous step process performed with a Novasep simulated moving bed system, was successfully approved by the US Food and Drug Administration (FDA).

Seal Sands project timescale

Construction of the production unit, designated P7, was set to a very tight schedule. The facility was built as a fast-track project. This required Foster Wheeler as project manager to foster a creative and flexible approach, particularly with subcontractors.

Pipe racks and other large-scale plants such as evaporators and filter driers were constructed off-site and then transported and fitted together as modules.

The plant was based on a skid-mounted modular principle, which cut down on the time used in on-site fabrication and allows equipment to be installed in a very short time-scale and also allows flexibility if expansion is required at a later date.

The plant was completed, validated and in full production by January 2003, which fulfilled the set time schedule. P7 is a high-tech synthesis factory that has been designed to meet an aim of low environmental impact from production.