Ferring Pharmaceuticals of Kiel, Wittland, Germany – a subsidiary of Ferring BV of Switzerland – began construction of a new pharmaceutical production facility on an existing 25,800m² production site near Kiel, Germany, in August 2003.
The plant was called the NFF production facility (New Freeze Drying and Filling), and now freeze dries and fills some of Ferring’s most successful products, including Desmopressin acetate (a vasopressin analogue), Bravelle (a highly purified
preparation of human follicle stimulating hormone (FSH) [fertility treatment]) and the new potential blockbuster, Degarelix, which is a drug for the treatment of prostate cancer. Phase III trials ended in December 2007 and an NDA was submitted in first quarter of 2008, with the product due to be launched in 2009.
The investment into the plant, which employs 160 personnel, was estimated at more than €10m and has more than doubled the company’s previous freeze-drying capacity to allow a significant increase in production.
The new plant was constructed within 17 months and was completed in January 2005 (construction actually finished in October 2004 but fitting out took until January 2005). However, the new facility had to go through many months of commissioning and validation before commercial-scale production could begin. Production at the site started in the second half of 2005.
CONTRACTORS AND CONSTRUCTION
The architects for the project were Holle Paulsen and Wolf Schellwien (engineer) of Hoff Partner architects. The turnkey contract for the engineering, construction and outfitting of the plant was awarded to LSMW GmbH, a subsidiary company of M+W Zander, which is part of Jenoptik’s Clean Systems business division.
In addition to the construction of the facility and the services and technical infrastructure, the order included the delivery and assembly of the specialist cleanroom technology and production equipment for the 4,600m², four-storey building, including the final qualification and validation of the facility.
The project was completed on time and within budget in just 17 months, which was unexpected as the processing machines were not delivered until 12 months into the project.
Ferring now uses the new production plant for bottling sterile solutions aseptically in vials, subsequently freeze-drying, sealing and alu-capping them. The central process of the plant consists of a high-performance filling machine, coupled to a fully-automatic charging system for the freeze-dryer. The level of automation of the plant is very high, thus minimising risks such as possible contamination caused by human intervention in the production process. Wherever possible, production stages are carried out in closed systems.
The first floor of the new building houses the production plant for freeze-drying and filling. The production area has a ceiling height of approximately 6.00m so that following fitting out of the production equipment in a suspended fashion (for reasons of little or no human contact, which could cause contamination) all maintenance at the complex can come from above without restricting the production. The floor surface of this installation is also designed as cleanroom.
The new production plant is connected by a bridge to the warehousing and storage areas of the existing facility. The ground floor houses the service and technical infrastructure. The upper floors are used as additional office space for the company.
The new building has been constructed in keeping with the style of the existing buildings (1 and 2). The front of the new facility is constructed with special wall details and has a glass walled elevator on the north side. The glass facade panels of the building’s upper floor are specially designed with wing-like aluminium lamellae for sun and wind protection, which reduces the strain on any HVAC (heating, ventilation and air conditioning) system in the building.
The NFF production facility (New Freeze Drying Facility) fills and freeze dries pharmaceutical products in accordance with the latest regulations of current Good Manufacturing Practice (cGMP) and the US FDA regulations.
Freeze drying is a process that plays an increasingly important role in the pharmaceutical / biotech industry, especially for biotechnologically-produced products. The process to be employed, known as lyophilisation, is an optimal drying method which extends the lifetime of temperature-sensitive medicines.
Lyophilisation or cryodessication is able to remove moisture or alcohol at low temperature from pharmaceuticals without destroying the physical structure. The material is frozen and then under a vacuum the ice sublimes with no introduction of heat save the ambient conditions. The moisture is trapped in a cold trap and the resulting product is dried very gently.
Ferring’s operations at Kiel include aseptic manufacturing operations, freeze drying, and microencapsulation of pharmaceuticals. The company also carries out analytical and microbiological testing of starting materials, intermediates and bulk.
The products from the facility are used in the therapeutic areas of infertility, endocrinology and urology. Products for infertility include: Menopur, Menogon, Choragon and Decapeptyl for urology Decapeptyl depot and for endocrinology Zomacton.