Amgen Pharmaceutical Manufacturing Facility, West Greenwic... http://www.pharmaceutical-technology.com/projects/westgreen...

Amgen Pharmaceutical Manufacturing Facility, West

Greenwich, Rhode Island, USA
Email Article Print Link To Us Related Projects

Key Data
Start year 2000 (retrofit project approval)
Project type Pharmaceutical production facility
Location West Greenwich, Rhode Island, USA
Estimated investment $700m plus
Completion 2005 validation, 2006 start of operations
Sponsor Amgen, Immunex
Full specifications

West Greenwich, Rhode Island, US, is the site of a new pharmaceutical manufacturing
facility dedicated to the production of Immunex's rheumatoid arthritis drug, Enbrel.
Although the continuation of the project was briefly put in doubt when the takeover
of Immunex by Amgen was proposed, the continuation of construction was one of the
conditions of the deal.

The completed pharmaceutical plant is now one of the biggest mammalian protein
Expand Image
manufacturing plants in the world. The project involved the retrofit of an existing
Immunex decided to
facility (BioNow project), and the construction of an entirely new manufacturing
purchase an existing
plant as well (the BioNext project). Both plants use Immunex's T1 Enhanced Process
manufacturing facility in
developed by the Immunex Process Science Group.
West Greenwich, and
HARD TIMES FOR retrofit it to produce the
AMGEN Enbrel drug.

In March 2007 Amgen

announced that there were
problems with two of its
drugs: Epogen and Aranesp
are both erythropoiesis-
stimulating agents (ESAs)
that are used to treat
chemotherapy-induced
anaemia among other
conditions. Studies
indicated that patients
taking the drugs to attain
higher haemoglobin levels
were more likely to suffer
from serious cardiovascular
events.

Amgen suffered from a sharp decline in sales for its ESA medications that resulted in Expand Image
a serious drop in profits and a slump in sales even for the very successful arthritis Work on the BioNext project
drug Enbrel. These problems have led to Amgen instigating a cost cutting programme in West Greenwich began in
which will see the laying off of 1,500 employees across all of its operation to cut November 2001.
costs by $1.9bn.

The effect on Rhode Island is the loss of 300 employees with the closure of the
BioNow building (scheduled to close by the end of 2007). Originally there had been
450 redundancies planned at the Rhode Island facility but sales of Enbrel improved in
the third quarter of 2007 to $821m up from $705m for the same period in 2006.

1 of 4 3/27/11 12:43 PM
Amgen Pharmaceutical Manufacturing Facility, West Greenwic... http://www.pharmaceutical-technology.com/projects/westgreen...

The ESA problems have been addressed by the commissioning of new clinical studies
into safety and by an improvement in the warnings included with the two drugs
Epogen and Aranesp. The BioNext plant is to be kept open to supply the market with
Enbrel.

WATER DISPUTE
In 2005 a dispute arose between Amgen and Kent County Water Authority over the
plant's demand for water. At that time the plant was already using 500,000 gallons
per day. Amgen wanted over 800,000 gallons per day for the plant and the authority Expand Image
said it could not be done. Part of the utilities
infrastructure at the new
The disagreement escalated and eventually in January 2006 the State passed a bill BioNext mammalian protein
guaranteeing the water supply for the company and forcing Kent County water manufacturing facility.
authority to back down. Amgen then had its engineers design and build a state-
of-the-art wastewater recycling plant and also a water conservation system that has
cut the plant's water usage by 160,000 gallons per day.

BIONEXT PROJECT (NEW ENBREL MANUFACTURING PLANT)

The second stage of the project involved building a new manufacturing plant. The
BioNext facility included a production building, a warehouse, a central utility plant
(47,000ft²), and a quality laboratory. The area covered was 500,000ft², and the
estimated cost was $500m.

The new facility houses nine bioreactors with a capacity of 20,000l each. This is
about ten times the size of bioreactors currently used in most pharmaceutical
manufacturing plants. The new manufacturing plant received FDA approval in a 2005
validation audit and is now in full production.

The BioNext plant employs 350 workers to give a total

of 700 personnel employed on the site. Ground was
"In 2005 a
Expand Image
broken for the BioNext project in November 2001. The dispute arose Immunex has also recently
project was executed in a fast track mode (33 months invested in a pharmaceutical
conceptual design through to mechanical completion) between Amgen facility in Bothell in
with extensive use of modularisation and off-site
fabrication. and Kent County Washington.

The plant is dedicated for human therapeutics

Water Authority
production, including upstream and downstream over the plant's
processing. The facilities include media/buffer prep,
inoculum prep, mammalian cell culture, harvest and demand for
purification.
water."
WEST GREENWICH BIONEXT PLANT
CONTRACTORS
Edward Rouse Architects designed the new pharmaceutical facility and Kvaerner
Engineering and Contracting had a key role in designing and building it. Turner
Construction was initially appointed as construction manager but was replaced in
2002 by Fluor.

Kinetics Group Inc was involved in the design and process engineering of the
equipment skids and additional equipment in the facility. Other process equipment
suppliers included: bioKinetics, a subsidiary of Alfa Laval, (process equipment Expand Image
design), Kinetics Modular Systems (smaller bioreactors – 3,000l and 15,000l – and the Part of an interim Enbrel
harvest module), Cascade Controls (automation, including Delta V installation), Tote manufacturing site at West
Systems International (solids handling systems – media and buffer powder), and ITT Greenwich owned by Wyeth-
Industries' Pure-Flo Solutions Group (ultra hygienic valves and skids). Ayerst Pharmaceuticals and
using Immunex's process
ADP Marshal (one of the BioNext project managers) and the 21st Century Labor technology.
Management Partnership were instrumental in setting up a successful Project Labour
Agreement (PLA) for the construction project. E2 Engineers were the structural
engineers for the construction of the QC laboratories.

2 of 4 3/27/11 12:43 PM
Amgen Pharmaceutical Manufacturing Facility, West Greenwic... http://www.pharmaceutical-technology.com/projects/westgreen...

PROJECT SPECIFICS
During conceptual design, bioKinetics used their K-TOPS software to model the new
plant systems and were able to demonstrate that production goals could be met with
only one harvest and purification train. They were also able to minimise the number
of prep tanks and CIP skids by suggesting the use of pre-sterilised plastic bags.

Their knowledge of bioreactor design and construction allowed the elimination of

over half of the I/O and piping found on similar equipment in the existing facility.
These economies of design saved $100m in construction cost and reduced the project
schedule by many months.

Ultra hygienic valves and skids from ITT Industries' Pure-Flo Solutions Group were
Expand Image
chosen for use in the manufacturing process. Over 3,000 Pure-Flo valves have been
The plant is now fully
installed in the West Greenwich facility on the upstream side, ranging in size from
operational.
0.5in to 4in.

The valves have been used in dozens of cell culture

"The retrofitted applications throughout the seed and production
Enbrel plant was bioreactor systems.

completed in Downstream applications at the plant, such as ultra-

filtration (UF), used traditional and custom zero-static
2001 and valves with sizes ranging from 0.5in to 3in. In
chromatography, PFSG 5-way chromatography valves,
validated for divert valves, by-pass valves and double block and vent
use in the valve blocks were used in critical control applications.

production of Over 500 PFSG valves, including the new ISG valve, were
employed in cryogenic vessels, which are used to control
Enbrel by the freezing, thawing and storage of biological products in
portable vessels. The ISG was selected due to its
FDA in 2002." internal design, which minimises contact surfaces and
hold up volumes.

RETROFITTED DRUG MANUFACTURING FACILITY Expand Image

The water treatment plant
Immunex agreed to take over an existing manufacturing facility from American Home will use 800,000 gallons per
Products' sub-division, Greenwich Holdings (BioNow project). The idea was that this day.
facility would be retrofitted to produce biotech pharmaceutical products. The
existing facility covers approximately 250,000ft² and is equipped with eight 8,000l
bioreactors.

The retrofit involved the adoption of: 120 pieces of major equipment, 25 miles of
pipe, 240 miles of electrical wire and 300t of heating and cooling ducts. The
retrofitted Enbrel plant was completed in 2001 and validated for use in the
production of Enbrel by the FDA in 2002. The total cost of the project was $225m.

Related links
Safety Plan for Potentially Dangerous Cancer Drugs

Related Projects: Americas

Unilife Corporation Commercial Production Facility,
Blu Pharmaceuticals Facility
Pharmatek Laboratories cGMP Facility
Ash Stevens Riverview Facility
Fraunhofer Plant-Based Vaccine Factory,

Post to: Delicious Digg reddit Facebook StumbleUpon

3 of 4 3/27/11 12:43 PM
Amgen Pharmaceutical Manufacturing Facility, West Greenwic... http://www.pharmaceutical-technology.com/projects/westgreen...

4 of 4 3/27/11 12:43 PM